Efficacy of Flowable Collagen Hemostat Evaluated in Preclinical Models of Liver Injury and Spinal Cord Exposure

Abstract

Introduction

Excessive bleeding in trauma and surgical settings leads to increased operative time, reoperation rates, and overall healthcare costs. A wide range of hemostatic agents have been developed to control bleeding that can vary considerably in type of hemostatic action, ease of application, cost, risk of infection, and dependence on patient coagulation. Microfibrillar collagen-based hemostatic materials (MCH) have yielded beneficial results in a variety of applications.

Methods

A new flowable collagen product, containing a modified MCH flour, but in a more convenient flowable delivery system, was evaluated for hemostatic efficacy in preclinical models of solid organ injury and spinal cord exposure. The primary objective of this study was to compare the hemostatic potential and local tissue responses to this novel, flowable collagen-based hemostatic agent to the original flour formulation to confirm that the new method of delivery did not interfere with the hemostatic properties of the MCH flour.

Results

When observed visually, the flowable MCH flour mixed with saline (FL) provided more precise application and uniform coverage to injured tissues compared to the dry MCH flour alone (F₀). All of the treatments (FL, F₀, and gauze) exhibited comparable Lewis bleed grade at all three time points evaluated in the capsular resection liver injury model (bleed grade: 1.0–1.3; p> 0.05 in all cases). FL and F₀ exhibited comparable 100% acute hemostatic efficacy and similar long-term histomorphological properties (up to 120 days) in a capsular resection liver injury in pigs, while gauze resulted in significantly lower rates of acute hemostatic efficacy (8–42%, p<0.05 in all cases). In an ovine model of dorsal laminectomy and durotomy, FL and F₀ again exhibited comparable results without any neurological effects.

Conclusion

Flowable microfibrillar collagen was shown to yield favorable short- and long-term outcomes in two representative applications where hemostatic efficacy is critical to surgical success.

Keywords:

• hemostatic agent
• bleeding
• microfibrillar collagen
• liver injury
• spine surgery

Disclosure

Dr. Bradbury, Mrs. Gagne and Dr. Badhwar are employees of BD. Dr. Lake is a consultant for and Dr. Deeken is the owner of Covalent Bio, LLC, which received funding from BD for this project. Dr. Bohnen is a consultant for BD. Dr. Deeken reports consulting fees from BD for manuscript preparation, during the conduct of the study; she also reports consulting fees for unrelated projects from BD, Medtronic, SurgiMatrix, Tissium, Surgical Innovation Associates, Osteogenics, Polynovo, MedSkin Solutions, Aran Biomedical, Ethicon (Johnson & Johnson), Americas Hernia Society Quality Collaborative, Colorado Therapeutics, and TELABio, outside the submitted work; In addition, Dr. Deeken has patents in bionanocomposite materials broadly related to the field of hernia repair (patent numbers: 2009293001, 2334257 2,334,257UK 602009046407.8, 2,334,257FR, 16/043,849, 2,737,542) issued to University of Missouri. The authors report no other conflicts of interest in this work.

Additional information

Funding

This project was funded by Becton, Dickinson, and Company (BD).